Regulatory elements and transcription factors of coregulated genes

To predict common regulatory elements (REs) for our input genes, we used a web server called DiRE (Distant Regulatory Elements of coexpressed genes, http://dire.dcode.org/), which is based on the Enhancer Identification (EI) method for predicting distant regulatory elements in higher eukaryotic genomes. DiRE predicts function-specific REs and scores the association of individual transcription factors (TFs) with the biological function shared by the group of input genes [37]. We selected a random set of 5,000 genes in the genome of mm9 (Mus musculus9) as the source of background genes. TF occurrence for the centage of candidate REs which contain a conserved binding site for a special TF and TF importance for the product of TF occurrence and TF weight were two major parameters of our predicted TFs. The candidate associated TFs with the value of TF importance more than 0.05 would be selected.